Respiratory syncytial virus is the most important cause of acute airway infections in infants and young children. By the age of two nearly all children will have undergone at least one respiratory syncytial virus infection. Although usually causing only mild disease, in a fraction of patients (1-2%) RSV infection leads to serious bronchiolitis where hospitalization is required. It has been estimated that each year 160,000 children die due to RSV infection. No effective prophylactic vaccine and no RSV-specific therapeutic small molecule are clinically developed. The only way in which high-risk infants can be partially protected from a severe disease caused by an anticipated RSV infection is by monthly injections with a humanized mouse monoclonal antibody directed against the pre- and postfusion conformation of the F protein of RSV (palivizumab). Nevertheless, treatment with this antibody is expensive and only used in a prophylactic setting. Several other RSV F protein binding agents are being developed, including prefusion specific monoclonal antibodies (Gilmans et al., 2015; McLellan et al., 2013), and a RSV F protein binding ISVD. However, the described ISVD has weak neutralization activity against RSV serotype B and/or multivalent formatting is needed to render the ISVD potent (WO2009147248; WO2010139808; WO2011064382; Schepens et al., 2011; Hultberg et al., 2011).
Recently, it was shown that conventional antibodies that specifically bind to the prefusion conformation of the RSV F protein are much more potent in vitro RSV neutralizers than antibodies that bind both the post- and the prefusion conformation of F (WO2008147196, US2012070446, McLellan et al., 2013). However, conventional antibodies can be cumbersome to produce and their stability may be limited. Furthermore, due to their relatively large size conventional antibodies can be hindered in their cognate epitope recognition in complex samples or when other antibodies and ligands are occupying sites in the vicinity of their epitopes.
Accordingly, and as there is no widely accepted treatment available, there is an unmet need for a potent anti-RSV drug which can be used for effective treatment and/or prevention of RSV infections.